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Michal L. Melamed, MD, MHS; Erin D. Michos, MD, MHS; Wendy Post, MD, MS; Brad Astor, PhD

Arch Intern Med. 2008;168(15):1629-1637.

Background  In patients undergoing dialysis, therapy with calcitriol or paricalcitol or other vitamin D agents is associated with reduced mortality. Observational data suggests that low 25-hydroxyvitamin D levels (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown.

Methods  We tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the Third National Health and Nutrition Examination Survey (NHANES III) linked mortality files. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000.

Results  In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL [to convert to nanomoles per liter, multiply by 2.496]), while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models (adjusted for baseline demographics, season, and traditional and novel CVD risk factors), compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The adjusted models of CVD and cancer mortality revealed a higher risk, which was not statistically significant.

Conclusion  The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

Author Affiliations: Division of Nephrology, Department of Medicine, and Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Melamed); Divisions of Cardiology (Drs Michos and Post) and General Internal Medicine (Dr Astor), Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland; and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore (Drs Post and Astor).

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